Compounds and methods for modulating claudin-mediated functions

Abstract

Method for using modulating agents to enhance or inhibit claudin-mediated cell adhesion in a variety of in vivo and in vitro contexts are provided. Within certain embodiments, the modulating agents may be used to increase blood/brain barrier permeability. The modulating agents comprise at least one claudin cell adhesion recognition sequence or an antibody or fragment thereof that specifically binds the claudin cell adhesion recognition sequence. Modulating agents may additionally comprise one or more cell adhesion recognition sequence recognized by other adhesion molecules. Such modulating agents may, but need not, be linked to a targeting agent, drug and/or support material.

What is claimed is:  
     
       1. A cell adhesion modulating composition comprising: 
       (a) a polypeptide consisting of between 5-50 consecutive amino acids of SEQ ID NO: 471, wherein said polypeptide comprises the formula:  
       
         
           Trp-Gln-Aaa-Baa-Ala-Phe-Caa-Asp  (SEQ ID NO:1)  
         
       
        wherein Aaa, Baa and Caa indicate independently selected amino acid residues.  
     
     
       2. A cell adhesion modulating composition comprising: 
       (a) a polypeptide consisting of between 7-50 consecutive amino acids of SEQ ID NO: 471, wherein said polypeptide comprises the formula:  
       
         
           Trp-Gln-Aaa-Baa-Ala-Phe-Caa-Asp  (SEQ ID NO:1)  
         
       
        wherein Aaa, Baa and Caa indicate independently selected amino acid residues.  
     
     
       3. A cell adhesion composition comprising: 
       (a) a polypeptide consisting of between 8-50 consecutive amino acids of SEQ ID NO: 471, wherein said polypeptide comprises the formula:  
       
         
           Trp-Gln-Aaa-Baa-Ala-Phe-Caa-Asp  (SEQ ID NO:1)  
         
       
        wherein Aaa, Baa and Caa indicate independently selected amino acid residues.  
     
     
       4. A cell adhesion modulating composition according to any one of claims  1 - 3 , wherein the polypeptide comprises an amino acid sequence selected from the group consisting of: VTAFLD (SEQ ID NO:271), QVTAF (SEQ ID NO:272), QVTAFL (SEQ ID NO:273), QVTAFLD (SEQ ID NO:274), WQVTAF (SEQ ID NO:275), WQVTAFL (SEQ ID NO:276) and WQVTAFLD (SEQ ID NO:277). 
     
     
       5. A cell adhesion modulating composition that comprises a linear peptide consisting of no more than 50 consecutive amino acid residues of SEQ ID NO:471 and comprising the sequence N-Ac-WQVTAFLD-NH 2  (SEQ ID NO:50).